Point-of-Care Cardiac Markers

Point-of-care (POC) cardiac marker testing measures cardiac troponin I or T (and sometimes creatine kinase MB, myoglobin, B-type natriuretic peptide, N-terminal pro-BNP and D-dimer) in whole blood, plasma or serum at the bedside or in the emergency department, with results in 10 to 20 minutes.

Conventional POC troponin assays are less sensitive than central laboratory high sensitivity troponin (limit of detection 10 to 50 ng/L, compared with 1 to 5 ng/L), and need serial sampling at presentation, 3 hours and sometimes 6 hours.

High sensitivity POC troponin systems (limit of detection 1 to 5 ng/L, 99th percentile 10 to 30 ng/L) now allow rapid rule out at 0 and 1 to 3 hours with negative predictive value over 99%, where validated.

Chest pain accounts for 5 to 10% of emergency visits, and acute myocardial infarction is diagnosed in 10 to 20% of those presenting with suspected acute coronary syndrome.

Troponin is the biomarker of choice for myocardial injury, and the diagnosis of myocardial infarction requires a rise and fall in troponin with at least one value over the 99th percentile upper reference limit and symptoms, ECG changes, imaging evidence or thrombus.

B-type natriuretic peptide supports diagnosis and prognosis in heart failure (acute breathlessness), and D-dimer helps exclude pulmonary embolism and aortic dissection in low risk patients.

Indications. Suspected acute coronary syndrome (chest pain, anginal equivalents, breathlessness, syncope, arrhythmia). Breathlessness with suspected heart failure (BNP or NT-proBNP). Suspected pulmonary embolism in low probability patients (D-dimer). Pre-hospital and rural settings where a laboratory is distant. Triage of undifferentiated emergency presentations.

Post-operative, post-procedure or chemotherapy cardiac monitoring. Myocarditis, pericarditis and cardiotoxicity assessment. Not to be used alone, without ECG and clinical assessment.

Specimen. Whole blood from a finger prick or venous sample (EDTA or lithium heparin, 0.15 to 0.25 mL, cartridge dependent), plasma or serum. Time of symptom onset and sample times are recorded, since troponin rises 2 to 3 hours after injury, peaks at 12 to 24 hours and remains elevated for 7 to 14 days. Strict adherence to the manufacturer's time and temperature requirements.

Repeat samples at 1 to 3 hours (high sensitivity assays) or 3 to 6 hours (conventional) after presentation, or later if symptoms continue.

Reference values. Troponin under the assay specific 99th percentile upper reference limit (conventional assays: about 0.03 to 0.05 microgram/L for troponin I; high sensitivity assays: about 14 to 34 ng/L, lower in women). BNP under 100 ng/L and NT-proBNP under 125 ng/L (under 300 ng/L for acute heart failure rule out). D-dimer under 500 ng/mL fibrinogen equivalent units (age adjusted: age times 10 ng/mL over 50 years).

Interpretation.

• Troponin over the 99th percentile with a rise and fall pattern and symptoms or ECG changes: acute myocardial infarction. ST elevation myocardial infarction is diagnosed on ECG, and reperfusion is not delayed by troponin results.
• Troponin elevated without rise and fall (stable): chronic myocardial injury (renal failure, heart failure, left ventricular hypertrophy, diabetes, structural disease).
• Troponin elevated with a rise and fall but no ischaemia: acute myocardial injury (myocarditis, pulmonary embolism, sepsis, tachyarrhythmia, stroke, cardiac contusion, cardiotoxic drugs, Takotsubo syndrome, aortic dissection, critical illness, intense exercise).
• Rapid rule out: very low troponin (under the limit of detection) at presentation more than 3 hours after symptom onset, or a low value with a small change at 1 to 3 hours, safely excludes myocardial infarction in most patients with a normal ECG.
• Rule in: high initial troponin (over 5 times the 99th percentile) or a large change within 1 to 3 hours.
• Observe zone (neither rule out nor rule in): further serial troponin, imaging and risk scores.
• BNP over 400 ng/L or NT-proBNP over 450 ng/L (age under 50 years), 900 ng/L (50 to 75 years), 1800 ng/L (over 75 years): acute heart failure likely. Values under the rule out limit make heart failure unlikely. Obesity lowers, and renal failure, atrial fibrillation and age raise values.
• Positive D-dimer: nonspecific (pregnancy, cancer, infection, surgery, age, inflammation), so imaging is required if clinical probability is intermediate or high.
• CK-MB and myoglobin add little to troponin and are rarely used now.

Critical values and findings needing immediate action.

• Chest pain with ST elevation or new left bundle branch block: immediate reperfusion (primary angioplasty or fibrinolysis), without waiting for troponin.
• Positive troponin with ongoing pain, haemodynamic or electrical instability, or heart failure: immediate coronary care, antiplatelet and anticoagulant therapy, and early invasive strategy.
• Rising troponin with ECG changes in a patient on cardiotoxic chemotherapy, or with myocarditis features: cardiology review and echocardiography.
• High troponin in a patient with tearing chest or back pain, pulse deficit or hypotension: aortic dissection, urgent imaging (anticoagulation withheld).
• Troponin positive in pulmonary embolism with hypotension: right ventricular strain, consider thrombolysis.
• Rule out result with continuing high risk features (unstable pain, dynamic ECG changes, syncope): admit and repeat testing.

Interferences and pitfalls.

• POC assays have lower analytical sensitivity and precision than laboratory high sensitivity assays, and the rule out algorithms are valid only for the validated assay and cut offs.
• Early presenters (under 3 hours from onset) with a single negative conventional troponin cannot be ruled out, and repeat testing is mandatory.
• Heterophile antibodies, rheumatoid factor, fibrin clots, macrotroponin, haemolysis, and biotin supplementation (high doses) cause false positives or negatives, depending on the assay design.
• Renal failure raises troponin and natriuretic peptides without acute coronary syndrome, so serial change rather than a single value is used.
• Sex specific cut offs for high sensitivity assays (lower in women) improve diagnosis in women, who are more often under diagnosed.
• Troponin elevation is not specific for coronary thrombosis (type 1 myocardial infarction), and type 2 infarction (supply demand mismatch) requires treatment of the cause.
• A normal troponin does not exclude unstable angina, and risk stratification (history, ECG, risk score) continues.
• BNP is raised by sacubitril (neprilysin inhibition), so NT-proBNP is used in treated patients.
• Quality control, operator training, temperature and storage of cartridges, and connectivity to the electronic record are required.
• Cost, access and need for confirmatory laboratory tests limit use in some settings.

Special groups.

• Women, older adults and diabetic patients: atypical symptoms (breathlessness, fatigue, nausea), and lower cut offs for women.
• Renal failure and dialysis: baseline chronically elevated troponin, so changes over time are used.
• Children and young adults: myocarditis, congenital heart disease and cardiotoxicity; adult cut offs do not apply.
• Pregnancy: troponin can be raised in pre-eclampsia, peripartum cardiomyopathy and coronary dissection.
• Critically ill and post-operative patients: frequent myocardial injury.
• Regions: POC troponin in primary care, rural hospitals and ambulances shortens time to treatment; rheumatic heart disease, cardiomyopathy and Chagas disease add to the burden in low income countries.

Follow up tests. 12-lead ECG (repeated and serial), laboratory high sensitivity troponin, echocardiography, full blood count, creatinine and eGFR, electrolytes, glucose, lipid profile, HbA1c, chest radiograph, CT coronary angiography or stress testing in low to intermediate risk, coronary angiography in high risk, cardiac MRI for myocarditis and Takotsubo syndrome,

CT pulmonary angiography or CT aortography if indicated, D-dimer, NT-proBNP, thyroid function, and viral and autoimmune tests in myocarditis.